The E. coli expression system is extensively used as the first choice in genetic engineering due to its high productivity, high growth and production rate, ease of use, and economy, etc. However when expressed in E. coli, most recombinant proteins deposit in the form of insoluble and inactive inclusion bodies. Although insoluble inclusion bodies can bring some convenience for the isolation process, biological activities of such inclusion bodies can be recovered only after in vitro process of denaturation and subsequent renaturation. In vitro renaturation is a complicated and low-efficient process. For proteins with multiple disulfide bonds, especially for pharmaceutical use, the removal of misfolded or partially misfolded proteins will bring more difficulties to the downstream purification process. Researchers usually attempt to improve the solubility or folding of recombinant proteins by a variety of means, such as co-expression of chaperone proteins, protein disulfide isomerase, or peptidyl-prolyl cis-trans isomerase and so on in vivo, growing the cells at lower temperatures, and using solubilizing fusion partners. Another commonly used method is fusion expression, by which the solubility and yield of target protein could be improved with the help of its fused partner, which is already known to be expressed well and highly soluble in E. coli. Most of the successful fusion protein systems are those employing glutathione S transferase (GST), E. coli maltose binding protein malE and E. coli thioredoxin (Trx). The fusion partner often provides a distinct biochemical property which can be exploited as an affinity tag for fusion protein purification. All the above mentioned alternatives have been widely applied to both academic research and pharmaceutical industry.